CDC NOWCAST Variant Proportions
Currently, the Centers for Disease Control and Prevention has classified SARS-CoV-2 BA.4 and BA.5 as ‘variants of concern’.3 The World Health Organization has classified BA.4 and BA.5 as ‘variant of concern lineages under monitoring’ (VOC-LUM). The current working definition for this classification is that the variant belongs to a current circulating variant of concern, shows signs of transmission advantage, and has additional amino acid changes known or suspected to change the epidemiology and fitness advantage compared to other circulating variants of concern.4
Reducing Transmission
In general, Omicron spreads easier than other variants. As of now, there is no indication that BA.4 or BA.5 have any increased risk of severe disease or death.3,5
Presently, CDC and WHO are still recommending tried and true COVID-19 prevention strategies such as vaccination, masking, testing, and treatment.6
Earlier this week, the Biden Administration released its guidance on managing BA.5. This strategy is consistent with previous recommendations and guidance.7
Vaccination Implications:
There are ongoing studies researching the effectiveness of current COVID-19 vaccines regarding these new subvariants. In a study evaluating neutralizing antibody titers of the reference and omicron subvariants, participants were vaccinated and boosted with Pfizer-BioNTech. It was found that there does seem to be a decrease in vaccine effectiveness for the BA.4 and BA.5 variants. This also indicates that reinfection for those who contracted COVID-19 previously may be more likely but this has not been proven.8,5 FDA has advised vaccine manufacturers to develop bivalent (two-component) vaccines with their current vaccine composition and to add an Omicron BA.4 an BA.5 component, which will hopefully be introduced this year.9
Treatment Implications:
Regarding treatment, bebtelovimab was approximately 2 times more effective against BA.2, BA.4, and BA.5 compared to the original strain.10 Bebtelovimab is authorized under an emergency use authorization from February 2022 and is to be used for mild to moderate COVID-19 in adults and pediatric patients.11 A fact sheet for provider is linked.12 There does seem to be a decrease in treatment effectiveness for cilgavimab, casirivimab, and imdevimab.5,10
Detailed Mutation Information:
The spike proteins of BA.4 and BA.5 are most similar to BA.2, except for additional mutations. It is currently unknown how these mutations will impact the phenotype. Based on the location and type of mutations, there will likely be an impact on the human angiotensin-converting enzyme-2 and antibody binding, an increased affinity for receptor binding resulting in increased infectivity, a reduction in neutralization by monoclonal antibodies and polyclonal sera. Studies have estimated BA.5 has a higher daily growth advantage than BA.4, but both are similar to BA.2 over BA.1 as was seen in February 2022.1
References:
1 Continued Emergency and Evolution of Omicron in South Africa: New BA.4 and BA.5 Lineages
2 CDC Variant Proportions
3 CDC Variants
4 WHO Variants
5 WHO Weekly Epidemiology Update
6 CDC Omicron Variant Recommendations
7 White House Strategy to Manage BA.5
8 Neutralization Escape by SARS-CoV-2 Omicron Subvariants BA.2.12.1, BA.4, and BA.5
9 FDA COVID-19 Booster Composition
10 Sensitivity of novel SARS-CoV-2 Omicron subvariants, BA.2.11, BA.2.12.1, BA.4 and BA.5 to therapeutic monoclonal antibodies
11 FDA Authorizes New Monoclonal Antibody for Treatment of COVID-19 that Retains Activity Against Omicron Variant
12 Bebtelovimab Health Care Provider Fact Sheet
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